Other Tracers 18F3Deoxy3Fluorothymid ine

The thymidine analog 18F-3'-deoxy-3'-fluorothymidinethymidine analog (F-18-FLT) is a promising tracer, now finding limited use as a proliferation marker. Originally, FLT was used as a chemotherapeutic agent, but abandoned due to severe side effects. FLT is currently used in its F-18 labeled form for both experimental and patient studies. Rasey et al. (30) evaluated F-18-FLT in cell culture studies using human lung carcinoma cells and noted that the tracer uptake correlates with the thy-midine kinase-1 activity with r2 = 0.63. The authors report an excellent correlation of r2 = 0.91 for the F-18-FLT uptake and the percentage of cells in S-phase. The comparison of F-18-FLT and C-14-DG (deoxyglucose) showed that an increase of the percent S-phase cells from 4% to 32% enhanced the F-18-FLT uptake by a factor of 6.4, while the C-14-DG uptake was only increased by 1.8 (30). The data show that DG is dependent on proliferation, but the uptake change varies according to the S-phase fraction and is generally lower. F-18-FLT is likely to be more accurate with regard to tumor proliferation (Fig. 7).

The accurate, noninvasive quantification of tumor proliferation requires a tracer which is incorporated into DNA. However, F-18-FLT is an indirect marker for proliferation, because the majority of the signal is obtained by the thymidine kinase-1 activity. Lu et al. (31) evaluated several radiotracers regarding their use as proliferation markers. The comparison of tracer kinetics demonstrates only for 1-(2'-deoxy-2'-fluoro-p-D-arabinofuranosyl)-5-[76Br]bromouracil (76Br-BFU), a continuous increase of tracer uptake with time. The DNA incorporation was highest for 76Br-BFU with 97%, 80% for 1-(2'-deoxy-2'-fluoro-p-D-arabinofuranosyl)-[methyl-11C]thymine (11C-FMAU), and only 2% for F-18-FLT. Cimetidine, which has an impact on the elimination of nucleosides, altered the uptake of 76Br-BFU, but not 11C-FMAU and F-18-FLT. The data show that the tumor proliferation can be measured with different accuracy. While 76Br-BFU is likely to reflect tumor proliferation most accurately, other tracers like F-18-FLT and FDG are also acceptable for patient studies because they are indirectly involved in the proliferation of cells.